The oocyte microenvironment is altered in adolescents compared to oocyte donors.
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ABSTRACT:
SUBMITTER: Gokyer D
PROVIDER: S-EPMC11361810 | biostudies-literature | 2024
REPOSITORIES: biostudies-literature
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The oocyte microenvironment is altered in adolescents compared to oocyte donors.
Gokyer Dilan D Akinboro Sophia S Zhou Luhan T LT Kleinhans Anna A Laronda Monica M MM Duncan Francesca E FE Riley Joan K JK Goldman Kara N KN Babayev Elnur E
Human reproduction open 20240806 3
<h4>Study question</h4>Do the molecular signatures of cumulus cells (CCs) and follicular fluid (FF) of adolescents undergoing fertility preservation differ from that of oocyte donors?<h4>Summary answer</h4>The microenvironment immediately surrounding the oocyte, including the CCs and FF, is altered in adolescents undergoing fertility preservation compared to oocyte donors.<h4>What is known already</h4>Adolescents experience a period of subfecundity following menarche. Recent evidence suggests th ...[more]
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Project description:Study question: Are the molecular signatures of cumulus cells (CCs) and follicular fluid (FF) of adolescents undergoing fertility preservation differ from that of reproductively adult oocyte donors? Summary answer: The microenvironment immediately surrounding the oocyte, including the CCs and FF, is altered in adolescents undergoing fertility preservation compared to oocyte donors. What is known already: Adolescents experience a period of subfecundity following menarche. Recent evidence suggests that this may be at least partially due to increased oocyte aneuploidy. Reproductive juvenescence in mammals is associated with suboptimal oocyte quality. Study design, size, duration: This was a prospective cohort study. Adolescents (10-19 years old, N=23) and oocyte donors (22-30 years old, N=31) undergoing ovarian stimulation and oocyte retrieval at the Northwestern Fertility and Reproductive Medicine Center between November 1, 2020 and May 1, 2023 were enrolled in this study. Participants/materials, setting, method: Patient demographics, ovarian stimulation, and oocyte retrieval outcomes were collected for all participants. The transcriptome of CCs associated with mature oocytes was compared between adolescents (10-19 years old, n=19), and oocyte donors (22-30 years old, n=19) using bulk RNA-sequencing. FF cytokine profiles (10-19 years old, n=18 vs. 25-30 years old, n=16) were compared using cytokine arrays. Main results and the role of chance: RNA-seq analysis revealed 581 differentially expressed genes (DEGs) in cumulus cells of adolescents relative to oocyte donors, with 361 genes downregulated and 220 upregulated. Genes enriched in pathways involved in cell cycle and cell division (e.g., GO:1903047, p= 3.5 x 10-43; GO:0051983, p= 4.1 x 10- 30; GO:0000281, p= 7.7 x 10-15; GO:0044839, p= 5.3 x 10-13) were significantly downregulated, while genes enriched in several pathways involved in cellular and vesicle organization (e.g., GO:0010256, p= 1.2 x 10-8; GO:0051129, p= 6.8 x 10-7; GO:0016050, p= 7.4 x 10-7; GO:0051640, p= 8.1 x 10-7) were upregulated in CCs of adolescents compared to oocyte donors. The levels of 9 cytokines were significantly increased in FF of adolescents compared to oocyte donors: IL-1 alpha (2-fold), IL-1 beta (1.7-fold), I-309 (2-fold), IL-15 (1.6-fold), TARC (1.9-fold), TPO (2.1-fold), IGFBP-4 (2-fold), IL-12-p40 (1.7-fold) and ENA-78 (1.4-fold). Interestingly, 7 of these cytokines have known pro-inflammatory roles. Importantly, neither the CC transcriptomes or FF cytokine profiles were different in adolescents with or without cancer. Large scale data: Original high-throughput sequencing data will be deposited in Gene Expression Omnibus (GEO) before publication, and the GEO accession number will be provided here. Limitations, reasons for caution: This study aims to gain insights into the associated gamete quality by studying the immediate oocyte microenvironment. The direct study of oocytes is more challenging due to sample scarcity, as they are cryopreserved for future use, but will provide a more accurate assessment of oocyte reproductive potential. Wider implications of the findings: Understanding the underpinnings of altered immediate oocyte microenvironment of adolescent patients may provide insights into the reproductive potential of the associated gametes in the younger end of the age spectrum. This has implications for the fertility preservation cycles for very young patients.
2024-05-15 | GSE265995 | GEO
Project description:The oocyte microenvironment is altered in adolescents compared to oocyte donors.
| PRJNA1105097 | ENA
Project description:ObjectiveThe follicular fluid (FF) of women with polycystic ovary syndrome (PCOS) seems to exhibit a profile different from that of fertile women, which may be related to folliculogenesis disruption in PCOS patients. The aim of this study was to evaluate the differentially expressed proteins in the FF of women with PCOS compared to oocyte donors (ODs).MethodsThis screening study included thirteen (13) women who underwent in vitro fertilization (IVF) cycles: seven (7) ODs and six (6) PCOS patients. The patients underwent standard ovarian stimulation, and the FF was analysed using ion trap and time-of-flight liquid chromatography-mass spectrometry (LCMS-IT-TOF).ResultsThe FF of the patients was matched to 229 proteins, with 61 proteins exclusive to the PCOS group, 123 proteins exclusive to the ODs, and 45 proteins found in both groups. We highlight fetuin-A and vitamin D ligand protein, which were exclusively expressed in the PCOS group; Complement C3 overexpressed in the PCOS group; and 26S protease only expressed in the OD group. The canonical pathways LXR/RXR activation, FXR/RXR activation, prothrombin activation are directly related to the disrupted metabolism and increased inflammatory status found in PCOS patients.ConclusionsThe findings of the differentially expressed proteins and matched pathways are associated with folliculogenesis, indicating it relevance to oocyte quality.
| S-EPMC6798591 | biostudies-literature
Project description:Concussion is a mild traumatic brain injury (mTBI) with increasing prevalence among children and adolescents. Functional connectivity (FC) within and between the default mode network (DMN), central executive network (CEN) and salience network (SN) has been shown to be altered post-concussion. Few studies have investigated connectivity within and between these 3 networks following a pediatric concussion. The present study explored whether within and between-network FC differs between a pediatric concussion and orthopedic injury (OI) group aged 10-18. Participants underwent a resting-state functional magnetic resonance imaging (rs-fMRI) scan at 4 weeks post-injury. One-way ANCOVA analyses were conducted between groups with the seed-based FC of the 3 networks. A total of 55 concussion and 27 OI participants were included in the analyses. Increased within-network FC of the CEN and decreased between-network FC of the DMN-CEN was found in the concussion group when compared to the OI group. Secondary analyses using spherical SN regions of interest revealed increased within-network FC of the SN and increased between-network FC of the DMN-SN and CEN-SN in the concussion group when compared to the OI group. This study identified differential connectivity patterns following a pediatric concussion as compared to an OI 4 weeks post-injury. These differences indicate potential adaptive brain mechanisms that may provide insight into recovery trajectories and appropriate timing of treatment within the first month following a concussion.
| S-EPMC9668608 | biostudies-literature
Project description:Studies in mice and older, subfertile women have found that air pollution exposure may compromise female reproduction. Our objective was to evaluate the effects of air pollution on ovarian reserve and outcomes of ovarian stimulation among young, healthy females. We included 472 oocyte donors who underwent 781 ovarian stimulation cycles at a fertility clinic in Atlanta, Georgia, USA (2008-2019). Antral follicle count (AFC) was assessed with transvaginal ultrasonography and total and mature oocyte count was assessed following oocyte retrieval. Ovarian sensitivity index (OSI) was calculated as the total number of oocytes divided by total gonadotrophin dose × 1000. Daily ambient exposure to nitric oxide (NOx), carbon monoxide (CO), and particulate matter ≤ 2.5 (PM2.5) was estimated using a fused regional + line-source model for near-surface releases at a 250 m resolution based on residential address. Generalized estimating equations were used to evaluate the associations of an interquartile range (IQR) increase in pollutant exposure with outcomes adjusted for donor characteristics, census-level poverty, and meteorological factors. The median (IQR) age among oocyte donors was 25.0 (5.0) years, and 31% of the donors were racial/ethnic minorities. The median (IQR) exposure to NOx, CO, and PM2.5 in the 3 months prior to stimulation was 37.7 (32.0) ppb, 612 (317) ppb, and 9.8 (2.9) µg/m3, respectively. Ambient air pollution exposure in the 3 months before AFC was not associated with AFC. An IQR increase in PM2.5 in the 3 months before AFC and during stimulation was associated with -7.5% (95% CI -14.1, -0.4) and -6.4% (95% CI -11.0, -1.6) fewer mature oocytes, and a -1.9 (95% CI -3.2, -0.5) and -1.0 (95% CI -1.8, -0.2) lower OSI, respectively. Our results suggest that lowering the current 24-h PM2.5 standard in the US to 25 µg/m3 may still not adequately protect against the reprotoxic effects of short-term PM2.5 exposure.
| S-EPMC10871039 | biostudies-literature
Project description:ObjectiveTo study the efficacy of estradiol for cycle programming in oocyte donors when administered in the follicular phase only.DesignProspective interventional study.SettingSingle fertility center.PatientsNinety-three oocyte donors underwent programmed stimulation using estradiol in the follicular phase. Their previous unprogrammed cycles were used as historical controls.InterventionsDonors received 8 mg of estradiol hemihydrate from day 2 till 1 day before the start of stimulation.Main outcome measuresThe primary outcome measures studied were the number of oocytes retrieved, duration of stimulation, and total gonadotropin dose. The number of mature oocytes, oocyte maturation rate, fertilization rate, blastulation rate, implantation rate, and pregnancy rate were the secondary outcomes.ResultsThe average number of oocytes retrieved was higher in the study group (36.4 vs. 32.5). The duration of stimulation (9.22 vs. 9.21 days) and the total gonadotropin dose were similar (3,085.5 vs. 3,026 IU) between both groups. The mean number of mature oocytes retrieved was higher in the study group (30.1 vs. 26.3), but the maturation rate was similar (84.6% vs. 81.2%). The fertilization rate (77.8% vs. 78.7%), number of blastocysts, blastulation rate (32.7% vs. 33.2%), implantation rate (59.3% vs. 66.3%), and pregnancy rate (77.3% vs. 77.1%) showed no statistically significant difference.ConclusionsEstradiol usage in the follicular phase alone is an effective and convenient option for cycle programming in oocyte donors. It can yield similar mature oocytes and does not affect the clinical outcomes. Further larger sample-sized studies may be needed to validate its use which can also be extended to routine in vitro fertilization cycles.Clinical trials registration numberCTRI/2020/09/027815.
| S-EPMC8978085 | biostudies-literature
Project description:PURPOSE:To examine the effect of low and very low estradiol responses in oocyte donors receiving gonadotropins on clinical outcomes of donor in vitro fertilization (IVF) cycles and to identify possible mechanisms responsible for low estradiol response. METHODS:This is a retrospective cohort study of oocyte donors undergoing antagonist IVF cycles with progression to oocyte retrieval between January 2010 and December 2016 at a single urban academic fertility center. Oocyte yield, fertilization rate, blastocyst rate, percentage of normal embryos on preimplantation genetic screening (PGS), pregnancy outcomes, and follicular fluid steroid profiles were compared between donors with normal estradiol response and those with low estradiol response. RESULTS:Three hundred sixty-six antagonist oocyte donor IVF cycles were identified: 42 cycles had a normal estradiol response (NE2), defined as peak serum estradiol (E2) of over 200 pg/mL per retrieved oocyte; 140 cycles had an intermediate estradiol response (iE2), defined as peak serum E2 between 100 and 200 pg/mL per retrieved oocyte; 110 cycles had a low estradiol response (LE2), defined as peak serum E2 between 50 and 100 pg/mL per retrieved oocyte; and 74 cycles had a very low estradiol response (vLE2), defined as peak serum E2 less than 50 pg/mL per retrieved oocyte. LE2 cycles resulted in a greater number of mature oocytes (22.4 vs. 13.6, p < 0.017), and fertilizations versus NE2 donors (18.5 vs. 10.7, p < 0.017), although the number of transferred or cryopreserved blastocysts were similar between groups (8.6, 6.9 vs. 4.8, p = 0.095, p = 1). The percentage of chromosomally normal embryos after PGS was similar between LE2, vLE2, and NE2 cycles (66.4, 71.8 vs. 63.1%, p = 0.99, p = 1). Pregnancy outcomes were similar between LE2, vLE2, and NE2 cycles. Serum AMH obtained on the day of peak E2 was similar to baseline serum AMH and did not differ between LE2 versus NE2 cycles. Follicular fluid E2 levels paralleled serum E2 levels and were lower in LE2 cycles versus NE2 cycles. CONCLUSION:The prevalence of very low E2 responses in donors appears to be high (20.2%). In contrast to autologous IVF cycles, LE2 does not portend poor outcomes in oocyte donors.
| S-EPMC6133823 | biostudies-literature
Project description:IntroductionHyperinsulinaemia and insulin resistance (IR) are strongly associated with obesity and are forerunners of type 2 diabetes. Little is known about metabolic alterations separately associated with obesity, hyperinsulinaemia/IR and impaired glucose tolerance (IGT) in adolescents.ObjectivesTo identify metabolic alterations associated with obesity, hyperinsulinaemia/IR and hyperinsulinaemia/IR combined with IGT in obese adolescents.Methods81 adolescents were stratified into four groups based on body mass index (lean vs. obese), insulin responses (normal insulin (NI) vs. high insulin (HI)) and glucose responses (normal glucose tolerance (NGT) vs. IGT) after an oral glucose tolerance test (OGTT). The groups comprised: (1) healthy lean with NI and NGT, (2) obese with NI and NGT, (3) obese with HI and NGT, and (4) obese with HI and IGT. Targeted nuclear magnetic resonance-based metabolomics analysis was performed on fasting and seven post-OGTT plasma samples, followed by univariate and multivariate statistical analyses.ResultsTwo groups of metabolites were identified: (1) Metabolites associated with insulin response level: adolescents with HI (groups 3-4) had higher concentrations of branched-chain amino acids and tyrosine, and lower concentrations of serine, glycine, myo-inositol and dimethylsulfone, than adolescents with NI (groups 1-2). (2) Metabolites associated with obesity status: obese adolescents (groups 2-4) had higher concentrations of acetylcarnitine, alanine, pyruvate and glutamate, and lower concentrations of acetate, than lean adolescents (group 1).ConclusionsObesity is associated with shifts in fat and energy metabolism. Hyperinsulinaemia/IR in obese adolescents is also associated with increased branched-chain and aromatic amino acids.
| S-EPMC7803706 | biostudies-literature
Project description:Metastatic bone disease is generally incurable and leads to pathological fractures, pain, hypercalcemia, spinal cord compression and decreased mobility. The skeleton is the major site of bone metastases from solid cancers, including breast and prostate carcinoma. Bone metastasis is facilitated by activation of bone-resorbing osteoclasts, terminally differentiated multinucleated cells formed by fusion from monocytic precursors. Cancer cells are known to produce specific factors that stimulate osteoclast differentiation and function. Of interest, cancer cells are also known to alter their own bioenergetics increasing the use of glycolysis for their survival and function. Such change in energy utilization by cancer cells would result in altered levels of cell-permeable metabolites, including glucose, lactate, and pyruvate. Osteoclast resorption is energy-expensive, and we have previously demonstrated that during differentiation osteoclasts actively adapt to their bioenergetics microenvironment. We hypothesize that altered bioenergetics state of cancer cells will also modify the bioenergetics substrate availability for the tissue-resident bone cells, potentially creating a favorable milieu for pathological osteolysis. The goals of this review are to analyze how metastasizing cancer cells change the availability of energy substrates in bone microenvironment; and to assess how the altered bioenergetics may affect osteoclast differentiation and activity.
| S-EPMC7290111 | biostudies-literature
Project description:PurposeThe target population for fertility preservation recently has been expanded from adolescents with cancer undergoing gonadotoxic chemotherapy to include transgender youth before initiating gender-affirming hormone therapy. Patients and providers may have knowledge deficits regarding options for fertility preservation, accessibility, and feasibility of its techniques, and impact of treatment on future fertility. This study describes outcomes of sperm cryopreservation in transgender male-to-female (affirmed female) youth and compares semen parameters with adolescents diagnosed with cancer.MethodsMedical records of transgender-affirmed female adolescents and adolescent males diagnosed with cancer who underwent sperm cryopreservation at the Fertility and Advanced Reproductive Medicine clinic of the University of Texas (UT) Southwestern Medical Center between March 2015 and March 2020 were reviewed. Demographic data were recorded and values for sperm parameters (volume, count, total count, motility (%), total motile) were collected. When available, hormone levels (luteinizing hormone, follicle-stimulating hormone, testosterone, and estradiol) and Tanner stages were also assessed. The two populations were compared using chi-square analysis and two-sample student's t-test. Data are presented as mean±standard deviation.ResultsWhile semen quality parameters trended lower in transgender youth compared with adolescents with cancer, there was no statistically significant difference between groups. While four out of 18 patients in the transgender group had azoospermia, mean semen quality parameters fell within normal adult reference ranges for both groups.ConclusionSperm cryopreservation for transgender youth and adolescents with cancer is feasible, inexpensive, and does not result in significant treatment delays. This information can improve counseling and access to these procedures, particularly in the transgender population.
| S-EPMC9829158 | biostudies-literature